The Modification of Xa-ATIII-Heparin Dynamics by Protamine Sulfate

Abstract EN

Heparin promotes the formation of 1∘ FXaα-ATIII and FXaβ-ATIII complexes from the free enzymes and antithrombin III.

It further stimulates the transformations of the 1∘ complexes into the corresponding 3∘ complexes.

Additionally, it stimulates the degradation of the 1∘ FXaα-ATIII and FXaβ-ATIII complexes into free FXaα, FXaβ and ATIIIM.

Protamine sulfate (PS) stimulates the transformation of FXaα into FXaβ and hence to FXaγ.

It also stimulates the transformation of the 1∘-, 2∘-, and 3∘- FXα-ATIII complexes into their corresponding β-complexes.

It further promotes the degradation of the 1∘ FXaα- and FXaβ-ATIII complexes into their corresponding 3∘- FXaα- and FXaβ-ATIII complexes, with the concommittant release of FXaγ.

The addition of PS to FXa/ATIII/H mixtures results in a reduction in free FXa, ATIII, and 1∘ Xa-ATIII complex formation, together with the concommittant increase in 3∘-FXa- ATIII complex formation and release of FXaγ.

The likeliest explanation of these results resides in the removal of the effective free heparin as a consequence of the generation of a stable heparin/PS salt upon the addition of the PS to the FXa/ATIII/H mixtures, thereby effectively lowering clotting times.